Optical Imaging of Cancer (eBook)

Contents 6
Contributors 8
Introduction 11
Part I Optical Imaging Principles 12
Optical Imaging of Cancer: Enhancing Detection and Resection 13
Limits of Resolution: Numerical Aperture and Conventional Microscopy 13
Fluorescence Imaging 14
Limits of Fluorescence Imaging: How Close Can Two Objects Be and Still Be Identifiable as Two Objects? 18
Confocal Laser Scanning Microscopy 21
Multiphoton Imaging 23
The Problem of the z-Axis 23
Fluorescence Applications 25
Immunohistochemistry and Immunofluorescence 25
Fluorescence Recovery After Photobleaching (FRAP) 26
Fluorescence Resonance Energy Transfer (FRET) 27
FRET Can Be Used to Determine the Distance Between Two Molecules 28
Fluorescence Lifetime Imaging Microscopy (FLIM) 29
Fluorescence Lifetime Measurement 30
Controls and Image Processing 32
The Future 32
References and Recommended Readings 33
Endoscopic Techniques for Optical Imaging 35
Introduction 35
Multidetector Computed Tomography 35
Conventional Pulmonary Imaging 36
Autofluorescent Bronchoscopy 36
Micro-optical Imaging Techniques 37
Confocal Endo-microscopy 37
Combination Strategies 37
Conventional Optical (Macro-optical) Imaging 38
Autofluorescence Bronchoscopy 38
Narrrow-Band Imaging 39
Qualitative Color Analysis 39
Fluorescein Bronchoscopy 40
Micro-optical Imaging 41
Optical Coherence Tomography 42
Confocal Endo-microscopy 43
Catheter-Based Confocal Microscopy (CBCM) 45
Catheter Navigation and Guidance 46
Summary and Future Direction 49
References 50
Design and Use of the Surgical Microscopein Fluorescence-Guided Surgery 59
Introduction 59
The Operating Microscope for Visualization of Blood Flow 59
Oncology Fluorescence-Guided Surgery of GBM (Glioblastoma Multiforme) Tumors 63
Design Considerations for Surgeons Interested in Designing Surgical Fluorescence Microscope Procedures 67
Fluorophores for Optical Imaging 69
Introduction 69
Definitions 69
Operational Characteristics of Fluorescent Probes 71
Excitation Spectrum and Extinction Coefficient 71
Emission Spectrum 73
Environment Sensitivity and Quenching 75
Size 77
Chemical and Physical Stability 78
Conjugation and Targeting 79
Distribution and Pharmacokinetics 80
Toxicity 82
Photostability 84
Conclusions and Prospectus 84
Notes 84
References 85
Part II Cancer Targeting Strategies 88
Overview of Cancer Detection and Monitoring Strategies 89
Introduction 89
Contrast Mechanisms and Properties of an Ideal Imaging Probe 91
Clinical Implementation of Optical Imaging 98
Optical Imaging in Context: Comparison to Conventional Modalities 100
Advantages and Distinctions of Fluorescence Imaging 102
Challenges for Clinical development 102
Economics and Regulatory Issues for Imaging Probe Development 103
Conclusions 103
References 104
The Application of Tissue Autofluorescence in Detectionand Management of Oral Cancer and Premalignant Lesions 109
Introduction 109
Biology Underlying Tissue Autofluorescence 110
Current Applications of Tissue Autofluorescence in the Management of Lung, Cervical, and Skin Cancers 114
Potential Clinical Utilities of Tissue Autofluorescence in Oral Cancer and Premalignant Lesions 116
Future Directions 121
References 122
Proteinase Optical Imaging Tools for Cancer Detectionand Response to Therapy 127
Introduction: Proteases and Cancer 127
Imaging Proteinases 130
Optical Imaging 131
Substrate-Based Imaging Agents 132
Small Molecule Activity-Based Probes (ABPs) for Proteases 135
ABPs for C-Clan Proteases 136
ABPs for S-Clan Proteases 137
ABPs for M-Clan Proteases 137
Imaging Protease Activity in Tumors 137
Imaging Cancer with ABP-Based Imaging Agents 138
Substrate-Based Imaging Agents in Cancer 139
Conclusion and Future Directions 140
References 141
Illustrating Molecular Events with Light: A Perspectiveon Optical Reporter Genes 147
Introduction 147
Optical Reporter Genes 148
Bioluminescence Reporters 148
Luciferase 148
Beetle Luciferases 148
Marine Luciferases 149
Bacterial Luciferases 149
Gaussia Luciferase 149
In Vivo Bioluminescence Imaging 150
Fluorescent Proteins 151
Green Fluorescent Proteins 151
Red Fluorescent Proteins 151
Development of Specialized Reporters 153
Modified Mammalian Two-Hybrid Reporter System 153
Fluorescence Resonance Energy Transfer 154
Bioluminescence Resonance Energy Transfer 154
Spilt Reporter System 154
Multimodality Reporters 155
Molecular Vectors 155
Plasmids 156
Viral Vectors 156
Adenoviruses 156
Retroviruses 159
Lentiviruses 159
Adeno-associated Viruses 160
Applications 161
Preclinical Applications 161
Tumor/Cancer Biology 161
Gene Therapy/Adoptive Therapy 162
Cell Trafficking 163
Clinical Application 163
Challenges and Future Directions 164
References 165
Part III Preclinical and Clinical Investigations 169
Optical Imaging of Primary Tumors 170
Introduction 170
Photodynamic Detection 170
Aminolevulinic Acid and Hexaminolevulinate 171
Clinical Studies Using Photodynamic Detection 172
Topical Administration 172
Oral Administration 174
Photodynamic Therapy (PDT) 175
Molecularly Targeted Contrast Agents 175
Mechanisms to Molecularly Target Tumors 175
Tumor-Specific Ligands 178
Antibodies 178
Potential Clinical Applications 180
Clinical Significance 180
Intraoperative Guidance 181
Head and Neck Squamous Cell Carcinoma 182
In Vivo Model to Determine Sensitivity and Specificity 183
Glioblastomas 186
Barriers to Clinical Practice 186
Summary 187
References 187
Nodal Staging of Cancer Using Diagnostic OpticalImaging Techniques 192
Introduction 147
Limitations of Conventional Techniques 193
Sentinel Lymph Node Assessment 194
Practice and Research of Technique to Image Nodal Disease 196
Lymphoscintigraphy and Isosulfan Blue Dye 197
Superparamagnetic MR Contrast Agents 197
US, MR, CT Lymphangiography Techniques 197
Radioimmunoscintigraphy Techniques 198
NIR Fluorescence Imaging 199
Approach and Methods 201
Comparison of Scintigraphy and NIR Fluorescence Imaging of Lymph Nodes in Breast Cancer Patients 202
Functional Lymph Imaging in Health and Disease 204
Radio- and Optical-Immunoscintigraphy for Cancer Nodal Staging 205
Conclusion and Summary 208
References 211
Optical Coherence Tomography for Cancer Detection 215
Introduction 215
Optical Coherence Tomography (OCT) 215
Clinical Applications 216
Translation of OCT Technology 217
Principles of OCT 217
Low-Coherence Interferometry 218
OCT System Performance 219
Oncological Tissue Optics and OCT Imaging 220
Clinical Oncology Applications 221
Breast Cancer 221
Breast Cancer Management and Scope for OCT Intervention 221
OCT Atlas of Breast Cancer 224
Intraoperative Tumor Margin Detection 226
Intraoperative Lymph Node Imaging 227
Needle-Biopsy Guidance 229
Gastrointestinal Cancers 230
Barrett's Esophagus 231
Colon Cancer 231
Bladder Cancer 232
Skin Cancer 234
Oral Cancer 235
Computer-Aided Tissue Classification, Multimodal Imaging, and Contrast Enhancement 236
Computer-Aided Diagnosis 236
Multimodal Optical Imaging 238
Enhancing Endogenous Contrast 240
Exogenous Contrast Agents for OCT 242
Barriers to Clinical Application 244
Summary and Outlook on Clinical Adoption 246
References 247
Optical Imaging of Cancer: Neuro-oncologic Applications 257
Introduction 257
Clinical Significance 257
Advances in Imaging 258
Current Options in Clinical Diagnostic Imaging of CNS Malignancies 258
In Vivo Optical Imaging in Neuro-oncology 259
Fluorescence Imaging 260
Photodynamic Therapy (PDT) 261
Near Infrared Fluorescence Reflectance Imaging (NIRF-i) 261
Bioluminescence Imaging 263
Quantum Dots 263
Bimodal Fluorescence and Bioluminescence Imaging 264
Summary 266
References 268
Index 271